Copper peroxide-triggered reactive nitrogen effectively enhanced synergistic chemodynamic-immunotherapy.

J Colloid Interface Sci

State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianj

Published: December 2025


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Article Abstract

Overcoming the limitations of chemodynamic therapy (CDT), constrained by the transient nature and limited bioavailability of reactive oxygen species (ROS), this study proposes a synergistic strategy integrating CDT with immunotherapy. We engineered a multifunctional nanocarrier, HMSN-Met@HA-CuO₂, leveraging CuO to amplify intracellular ROS generation and induce cuproptosis. Concurrently, metformin (Met) releases nitric oxide (NO), which scavenges ROS to generate more stable reactive nitrogen species (RNS). These RNS elicit sustained and irreversible damage to lipids, proteins, and deoxyribonucleic acid (DNA), resulting in potent tumor cell cytotoxicity and activation of an antitumor immune response. This work demonstrates the potential of an autonomously driven conversion from oxygen radicals to nitrogen radicals, coupled with the enhanced combinatorial application of CDT and immunotherapy, significantly improving antitumor efficacy.

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http://dx.doi.org/10.1016/j.jcis.2025.138301DOI Listing

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